METABOLISM OF TESTOSTERONE TRANS-4-N-BUTYLCYCLOHEXYL CARBOXYLATE, A HIGH POTENCY ANDROGEN, IN RODENTS AND PRIMATES - IN-VITRO STUDIES

Testosterone trans-4-n-butylcyclohexyl carboxylate releases continuous physiological levels of testosterone into the circulation of men or m onkeys over a period of 8 to 10 weeks from an intramuscular depot and may, therefore, be an agent of choice for androgen replacement therapy . The purpose of this study wasto investigate the metabolism of the es ter and its side chain. The ester was hydrolysed by blood sera of guin ea-pig, rabbit and rat, but not horse or man. It was slowly hydrolysed by rat and cynomolgus liver and the testosterone metabolites androste nedione and androstanediol were formed. Bucyclic acid (trans-4-n-butyl cyclohexyl carboxylate) was slowly metabolized to two metabolites, M1 and M2, by cynomolgus liver homogenates. The acid metabolites were ana lysed bychromatography and mass spectrometry after reaction with diazo methylpyrene toform fluorescent pyrenyl esters. When compared with syn thetic compounds usingthe criteria of chromatographic mobility and mas s spectral analysis, the polar metabolite was identified as hydroxy-4- n-butylcyclohexyl carboxylate. The less polar metabolite could not be definitively identified.